Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models

ABSTRACT Chikungunya virus (CHIKV) is a reemerging arbovirus capable of causing explosive outbreaks of febrile illness, polyarthritis, and polyarthralgia, inflicting severe morbidity on affected populations. CHIKV can be genetically classified into 3 major lineages: West African (WA); East, Central,...

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Autores principales:	Rose M. Langsjoen, Sherry L. Haller, Chad J. Roy, Heather Vinet-Oliphant, Nicholas A. Bergren, Jesse H. Erasmus, Jill A. Livengood, Tim D. Powell, Scott C. Weaver, Shannan L. Rossi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	alphavirus chikungunya vaccine Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1322b217afe64896baeace1609ca4eab
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spelling	oai:doaj.org-article:1322b217afe64896baeace1609ca4eab2021-11-15T15:53:26ZChikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models10.1128/mBio.02449-172150-7511https://doaj.org/article/1322b217afe64896baeace1609ca4eab2018-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02449-17https://doaj.org/toc/2150-7511ABSTRACT Chikungunya virus (CHIKV) is a reemerging arbovirus capable of causing explosive outbreaks of febrile illness, polyarthritis, and polyarthralgia, inflicting severe morbidity on affected populations. CHIKV can be genetically classified into 3 major lineages: West African (WA); East, Central, and South African (ECSA); Indian Ocean (IOL); and Asian. Additionally, the Indian Ocean (IOL) sublineage emerged within the ECSA clade and the Asian/American sublineage emerged within the Asian clade. While differences in epidemiological and pathological characteristics among outbreaks involving different CHIKV lineages and sublineages have been suggested, few targeted investigations comparing lineage virulence levels have been reported. We compared the virulence levels of CHIKV isolates representing all major lineages and sublineages in the type I interferon receptor-knockout A129 mouse model and found lineage-specific differences in virulence. We also evaluated the cross-protective efficacy of the IOL-derived, live-attenuated vaccine strain CHIKV/IRESv1 against the Asian/American CHIKV isolate YO123223 in both murine and nonhuman primate models, as well as the WA strain SH2830 in a murine model. The CHIKV/IRES vaccine provided protection both in mice and in nonhuman primate cohorts against Caribbean strain challenge and protected mice against WA challenge. Taken together, our data suggest that Asian/American CHIKV strains are less virulent than those in the Asian, ECSA, and WA lineages and that despite differences in virulence, IOL-based vaccine strains offer robust cross-protection against strains from other lineages. Further research is needed to elucidate the genetic basis for variation in CHIKV virulence in the A129 mouse model and to corroborate this variation with human pathogenicity. IMPORTANCE Chikungunya virus (CHIKV) is a reemerging human pathogen capable of causing debilitating and disfiguring polyarthritis, which can last for months to years after initial fever has resolved. There are four major genetic lineages of CHIKV, as well as two recently emerged sublineages, none of which have been evaluated for differences in virulence. Moreover, the ability of chikungunya vaccines to cross-protect against heterologous CHIKV lineages has not been explored. Therefore, we sought to compare the virulence levels among CHIKV lineages, as well as to evaluate the cross-protective efficacy of the CHIKV/IRESv1 vaccine candidate, in two different models of CHIKV infection. Our results suggest that, although significant differences in virulence were observed among CHIKV lineages, the CHIKV/IRESv1 vaccine elicits cross-lineage protective immunity. These findings provide valuable information for predicting the severity of CHIKV-associated morbidity in future outbreaks, as well as vaccine development considerations.Rose M. LangsjoenSherry L. HallerChad J. RoyHeather Vinet-OliphantNicholas A. BergrenJesse H. ErasmusJill A. LivengoodTim D. PowellScott C. WeaverShannan L. RossiAmerican Society for MicrobiologyarticlealphaviruschikungunyavaccineMicrobiologyQR1-502ENmBio, Vol 9, Iss 2 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	alphavirus chikungunya vaccine Microbiology QR1-502
spellingShingle	alphavirus chikungunya vaccine Microbiology QR1-502 Rose M. Langsjoen Sherry L. Haller Chad J. Roy Heather Vinet-Oliphant Nicholas A. Bergren Jesse H. Erasmus Jill A. Livengood Tim D. Powell Scott C. Weaver Shannan L. Rossi Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models
description	ABSTRACT Chikungunya virus (CHIKV) is a reemerging arbovirus capable of causing explosive outbreaks of febrile illness, polyarthritis, and polyarthralgia, inflicting severe morbidity on affected populations. CHIKV can be genetically classified into 3 major lineages: West African (WA); East, Central, and South African (ECSA); Indian Ocean (IOL); and Asian. Additionally, the Indian Ocean (IOL) sublineage emerged within the ECSA clade and the Asian/American sublineage emerged within the Asian clade. While differences in epidemiological and pathological characteristics among outbreaks involving different CHIKV lineages and sublineages have been suggested, few targeted investigations comparing lineage virulence levels have been reported. We compared the virulence levels of CHIKV isolates representing all major lineages and sublineages in the type I interferon receptor-knockout A129 mouse model and found lineage-specific differences in virulence. We also evaluated the cross-protective efficacy of the IOL-derived, live-attenuated vaccine strain CHIKV/IRESv1 against the Asian/American CHIKV isolate YO123223 in both murine and nonhuman primate models, as well as the WA strain SH2830 in a murine model. The CHIKV/IRES vaccine provided protection both in mice and in nonhuman primate cohorts against Caribbean strain challenge and protected mice against WA challenge. Taken together, our data suggest that Asian/American CHIKV strains are less virulent than those in the Asian, ECSA, and WA lineages and that despite differences in virulence, IOL-based vaccine strains offer robust cross-protection against strains from other lineages. Further research is needed to elucidate the genetic basis for variation in CHIKV virulence in the A129 mouse model and to corroborate this variation with human pathogenicity. IMPORTANCE Chikungunya virus (CHIKV) is a reemerging human pathogen capable of causing debilitating and disfiguring polyarthritis, which can last for months to years after initial fever has resolved. There are four major genetic lineages of CHIKV, as well as two recently emerged sublineages, none of which have been evaluated for differences in virulence. Moreover, the ability of chikungunya vaccines to cross-protect against heterologous CHIKV lineages has not been explored. Therefore, we sought to compare the virulence levels among CHIKV lineages, as well as to evaluate the cross-protective efficacy of the CHIKV/IRESv1 vaccine candidate, in two different models of CHIKV infection. Our results suggest that, although significant differences in virulence were observed among CHIKV lineages, the CHIKV/IRESv1 vaccine elicits cross-lineage protective immunity. These findings provide valuable information for predicting the severity of CHIKV-associated morbidity in future outbreaks, as well as vaccine development considerations.
format	article
author	Rose M. Langsjoen Sherry L. Haller Chad J. Roy Heather Vinet-Oliphant Nicholas A. Bergren Jesse H. Erasmus Jill A. Livengood Tim D. Powell Scott C. Weaver Shannan L. Rossi
author_facet	Rose M. Langsjoen Sherry L. Haller Chad J. Roy Heather Vinet-Oliphant Nicholas A. Bergren Jesse H. Erasmus Jill A. Livengood Tim D. Powell Scott C. Weaver Shannan L. Rossi
author_sort	Rose M. Langsjoen
title	Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models
title_short	Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models
title_full	Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models
title_fullStr	Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models
title_full_unstemmed	Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models
title_sort	chikungunya virus strains show lineage-specific variations in virulence and cross-protective ability in murine and nonhuman primate models
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/1322b217afe64896baeace1609ca4eab
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Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models

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